The evolution of top management: a forecast,

At head of title: Preliminary draft, for comment."Based upon a seminar given by the author at the Fourth IBM Personnel Research Conference, January 11, 1967.

The R & D factor in international trade and international investment of United States industries

Research program on the management of science and technology

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients

The Fermi GBM Gamma-Ray Burst Spectral Catalog: Four Years Of Data

In this catalog we present the updated set of spectral analyses of GRBs detected by the Fermi Gamma-Ray Burst Monitor (GBM) during its first four years of operation. It contains two types of spectra, time-integrated spectral fits and spectral fits at the brightest time bin, from 943 triggered GRBs. Four different spectral models were fitted to the data, resulting in a compendium of more than 7500 spectra. The analysis was performed similarly, but not identically to Goldstein et al. 2012. All 487 GRBs from the first two years have been re-fitted using the same methodology as that of the 456 GRBs in years three and four. We describe, in detail, our procedure and criteria for the analysis, and present the results in the form of parameter distributions both for the observer-frame and rest-frame quantities. The data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: Accepted for publication in ApJ

First-year Results of Broadband Spectroscopy of the Brightest Fermi-GBM Gamma-Ray Bursts

We present here our results of the temporal and spectral analysis of a sample of 52 bright and hard gamma-ray bursts (GRBs) observed with the Fermi Gamma-ray Burst Monitor (GBM) during its first year of operation (July 2008-July 2009). Our sample was selected from a total of 253 GBM GRBs based on each event peak count rate measured between 0.2 and 40MeV. The final sample comprised 34 long and 18 short GRBs. These numbers show that the GBM sample contains a much larger fraction of short GRBs, than the CGRO/BATSE data set, which we explain as the result of our (different) selection criteria and the improved GBM trigger algorithms, which favor collection of short, bright GRBs over BATSE. A first by-product of our selection methodology is the determination of a detection threshold from the GBM data alone, above which GRBs most likely will be detected in the MeV/GeV range with the Large Area Telescope (LAT) onboard Fermi. This predictor will be very useful for future multiwavelength GRB follow ups with ground and space based observatories. Further we have estimated the burst durations up to 10MeV and for the first time expanded the duration-energy relationship in the GRB light curves to high energies. We confirm that GRB durations decline with energy as a power law with index approximately -0.4, as was found earlier with the BATSE data and we also notice evidence of a possible cutoff or break at higher energies. Finally, we performed time-integrated spectral analysis of all 52 bursts and compared their spectral parameters with those obtained with the larger data sample of the BATSE data. We find that the two parameter data sets are similar and confirm that short GRBs are in general harder than longer ones.Comment: 40 pages, 11 figures, 3 tables, Submitted to Ap

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes